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My Take on New Ocular Screening Guidelines for Plaquenil

Oct 14, 2016 1:06 pm

A recent article published by the American Academy of Ophthalmology (AAO) presented new recommendations for screening of patients being managed with hydroxychloroquine (HCQ).

In this article, new recommendations were made that changed the previous monitoring paradigm. More importantly, it has repositioned hydroxychloroquine from one of the safest medications that rheumatologists use to a drug that can have potentially significant ocular morbidity (if used in doses greater than 5 mg per kilogram and or for prolonged periods of time).

It has become fairly common practice for most rheumatologists to recommend that patients being treated with hydroxychloroquine be seen for formal visual field evaluation once or twice a year to monitor for retinal toxicity. The previous AAO guideline recommended screening every 12 months. Of course the aim is avoid drug related retinal toxicity, which on ophthalmic examination, appears as the classic Bull’s eye change affecting the macula.

Once retinal toxicity from hydroxychloroquine occurs, it is thought that the retinal changes are permanent and the disease can progress even if hydroxychloroquine is stopped for 1 to 3 years.

Newer techniques for evaluation of retinal disease have been developed and these techniques can detect retinal toxicity earlier. Spectral Domain Optical Coherence Tomography (SD OCT) uses light to capture micrometer-resolution, three-dimensional images from within optical scattering media. Multifocal Electroretinopathy measures electrical responses of various cell types in the retina. It is thought that although the bull’s eye seen on ophthalmic exam represents a disruption of the pigmented part of the retina, it is the photoreceptors that are the targets of hydroxychloroquine toxicity.

Notably the new recommendations were based on a single study published in 2014 that evaluated the prevalence of and risk factors for hydroxychloroquine retinal toxicity. (Citation source (link is external))

The study was a Kaiser Permanente retrospective case-control study that examined 2361 patients who had used hydroxychloroquine continuously for at least 5 years according to pharmacy records and who were evaluated with visual field testing or spectral-domain optical coherence tomography.

The main outcomes were toxicity as determined by characteristic visual field loss or retinal thinning and photoreceptor damage. They also examined risk factors and prevalence.

The study findings revealed that when hydroxychloroquine was used at doses < 5mg /kg, the risk of retinopathy was:

< 1% in the first 5 yrs.
< 2% in 10 yrs.
20 % after 20 yrs.

There was a dose response, such that those receiving doses greater that 5 mg / kg had the greatest risk of retinal toxicity. Risk factors for retinopathy included higher doses and longer durations of use. Other major factors are concomitant renal disease, use of tamoxifen and prior retinal or macular disease.

Thus, the new AAO screening and follow-up recommendations are shown below.

Hydroxychloroquine Screening Recommendations

Baseline Screening

  • Fundus examination within the first year of use
  • Add visual fields and SD OCT if maculopathy is present

Annual Screening

  • Begin after 5 years of use
  • Sooner in the presence of major risk factors

*SD OCT: Spectral Domain Optical Coherence Tomography


These recommendations hinge on ONE single study and the one study and recommendations were developed without the input of a rheumatologist. I wonder if any of the authors in either of these papers has ever prescribed antimalarial therapy. A logistic regression analysis was used to define risk factors but it is unclear if there were sufficient number of patients to differentiate risk based on ethnicity and race or individual disease states. Toxicity was determined on the basis of visual field loss or retinal thinning and photoreceptor damage but not both.

I suggest that we view these recommendations as preliminary and not gospel. Although I concur with the data on using less than 5mg/kg per day for now, I would recommend continued vigilance for ocular toxicity once or twice a year. More importantly it is clear that data is required to form more concrete recommendations and better definitions of risk factors. This data exists in European databases and should be reviewed and published.

Ideally those practitioners who prescribe antimalarial medications (e.g., rheumatologists, dermatologists) should be involved in the process of developing useful and preventative guidelines.

Continue Reading (Citation

The author has no conflicts of interest to disclose related to this subject

Sergio Schwartzman, MD, is the Franchellie M. Cadwell Associate Professor of Clinical Medicine at Cornell Weill Medical College, and Associate Attending Physician at the New York Presbyterian Hospital and at the Hospital for Special Surgery in New York City. Dr. Schwartzman has authored or coauthored over 60 articles, abstracts, books, and book chapters concerning rheumatoid arthritis, lupus, autoimmune ophthalmic disease, and related topics. Dr. Schwartzman is the recipient of The Fellows Award presented by the Northeast Regional American Rheumatism Association and The Franchellie M. Cadwell Chair. His current research interests spans the spondyloarthritis group of diseases, including understanding the microbiome in this group of illnesses, defining and treating autoimmune diseases of the eye, including uveitis, vasculitis, scleritis, and autoimmune orbital inflammatory disease and rheumatoid arthritis.

Rheumatologists’ Comments

Dr Arthur Weinstein

| Oct 17, 2016 9:16 am

I agree with you Sergio. Also some insurance companies are balking at paying for those tests in patients with normal vision just for HCQ toxicity screening

Robert Kimelheim

| Oct 20, 2016 7:05 am

Patients have been receiving plaquenil 400 mg for years (especially SLE patients ) and with usual standard of follow up, the cited retinopathy complication of 2-20% is far beyond anything I have seen in my patient population, many of which have been on drug for 20 years. That said, I recently reduced dosing to

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